Andrzej Borkowski

The clinical implications of the prostate cancer prevention trial.

The Prostate Cancer Prevention Trial has been mentioned before in the Comment Section, but several questions were raised by the publication of the results of the trial. These are addressed here and the trial is described in some detail. This review is a good starting point for people interested in the chemoprevention of prostate cancer to review critically the results of the trial for themselves.

BRCA1 mutations and prostate cancer in Poland

Evidence to date that BRCA1 mutation carriers are at an increased risk of prostate cancer is mixed – both positive and negative studies have been published. To establish whether or not inherited variation in BRCA1 influences prostate cancer risk we genotyped 1793 men with prostate cancer in Poland and 4570 controls for three founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.45% of the cases and 0.48% of the controls (odds ratio=0.9; P=1.0). The odds ratios varied substantially by mutation. The 5382insC mutation is the most common of the three founder mutations. It was detected only in one case (0.06%), whereas it was seen in 0.37% of controls (P=0.06). In contrast, the 4153delA was more common in prostate cancer cases (0.22%) than in controls (0.04%) (odds ratio=5.1; 95% confidence interval: 0.9–27.9; P=0.1). The C61G mutation was also found in excess in cases (0.17%) compared with controls (0.07%) (odds ratio=2.6; 95% confidence interval: 0.5–12.7; P=0.5). Eight men with prostate cancer carried a mutation. Only one of these carried the 5382insC mutation, compared with 17 of 22 individuals with mutations in the control population (P=0.003). These data suggest that the 5382insC mutation is unlikely to be pathogenic for prostate cancer in the Polish population. The presence of one of the other alleles was associated with an increased risk for prostate cancer (odds ratio=3.6; 95% confidence interval: 1.1–11.3; P=0.045); in particular for familial prostate cancer (odds ratio=12; 95% confidence interval: 2.9–51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers varies with the position of the mutation.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland

The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20‐fold). The geographical and ethnic extent of this recurrent allele has not yet been determined.

Twenty years of experience with Krzeski’s cystovaginoplasty for vaginal agenesis in Mayer-Rokitansky-Küster–Hauser syndrome: anatomical, histological, cytological and functional results

To evaluate the long‐term anatomical results using the original method of vaginal reconstruction with a pedicled bladder flap (Krzeski’s cystovaginoplasty, CVP) in women with Mayer‐Rokitansky‐Küster–Hauser syndrome (MRKHS) and the evaluation of radiological, histological, cytohormonal and functional results of CVP.

ESWL in Hemophiliac Patients

Objective: To assess ESWL treatment of urolithiasis in patients with hemophilia, the frequency of hemorrhagic complications, and to determine the treatment outline.Patients and Methods: From 1991 to 1997, eleven patients with hemophilia were treated by ESWL for urolithiasis. Substitution of deficient coagulation factors was started on the day of treatment. Ultrasound examination was performed in all cases on the 1st day after the procedure in order to discover any potential hemorrhagic complications. Substitution withdrawal depended on the patients’ general status, lack of hematuria and the absence of signs of hemorrhage. Preliminary results were evaluated after 7–10 days on the basis of plain abdominal X–ray of the kidney, ureter and bladder and ultrasonography.Results: In total, 25 ESWL sessions were performed, 1–6/patient. Nine patients (81.8%) discharged stones, and 2 patients are being followed up. No hemorrhagic complications were observed.Conclusions: Substitution of deficient coagulation factors makes ESWL a safe method of urinary stone management in hemophiliacs. No hemorrhagic complications were seen in our patients. Substitution withdrawal may be based on the patients’ good general status, lack of hematuria and absence of signs of hemorrhage.

Long-Term Subjective Results of Marshall-Marchetti-Krantz Procedure

Objective: Retrospective, subjective evaluation of results of suprapubic vesicourethropexy (Marshall-Marchetti-Krantz procedure) for stress urinary incontinence. Material: A total number of 81 patient records operated between 1980 and 1994 at our institution were reviewed and questionnaires were mailed to them to estimate the success rate, period of continence, current complaints and patient satisfaction. Patients with primary incontinence constituted 73% of this group, the remainder of 27% being recurrent or persistent incontinence. Results: The response rate was 75% (60 cases) and this group was evaluated. Mean postoperative time was 9.9 (2–15) years at the time of assessment. Mean duration of continence was 78.5 months and was not influenced by prior hysterectomy or parity. Weak correlation was found between patients’ age and continence period. It was similar in patients operated in their 5th and 6th decades of life and was shorter in the 7th decade. Additional sutures placed between the anterior bladder wall and rectus fascia (Lapides modification) resulted in a longer continence period. Cure rates decreased with time and were 81, 77, 57 and 28% after 6, 12, 60 and 120 months respectively. In the incontinent group, 34% of patients described leakage degree as lesser than preoperatively and 65% required protection. As many as 90% of continent and 62% of incontinent women evaluated their urinary system status as better than preoperatively. 90% of continent and 69% of incontinent women would repeat surgery again. Conclusions: This procedure is characterized by a high 81% early postoperative success rate that decreases with time. Despite recurrence of stress incontinence, one third of patients declare lesser incontinence degree and do not require protection.

A common nonsense mutation of the BLM gene and prostate cancer risk and survival

BACKGROUND Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis. Mutations of the BLM gene cause another chromosomal instability clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating mutation of BLM (Q548X) has been associated with a 6-fold increased risk of breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer etiology and survival has not been investigated yet. METHODS To establish whether the Q548X allele of the BLM gene is present in Poland, and whether this allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with prostate cancer and 2604 controls. RESULTS Q548X was detected in 13 of 3337 (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7; 95% CI 0.3-1.4). A positive family history of any cancer in a first- or second-degree relative was seen only in 4 of the 13 (30%) mutation positive families, compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow-up was 49months. Survival was similar among carriers of Q548X and non-carriers (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%, compared to 72% for mutation-negative cases. CONCLUSIONS BLM Q548X is a common founder mutation in Poland. We found no evidence that this mutation predisposes one to prostate cancer or affect prostate cancer survival. However, based on the observed 0.6% population frequency of the Q548X allele, we estimate that one in 100,000 children should be affected by Bloom syndrome in Poland.

P27(Kip1) and Ki-67 expression analysis in transitional cell carcinoma of the bladder.

P27Kip1 protein is a cell cycle inhibitor which blocks the transition of cells from G1 to S phase, while Ki-67 is the most specific marker of proliferative activity. Both proteins are independent predictors of clinical outcome in various neoplasms. The aim of the study was to assess the prognostic value of p27Kip1 and Ki-67 expression in urothelial bladder tumours. P27Kip1 and Ki-67 expressions were evaluated immunohistochemically in archival samples of 45 superficial and 26 invasive transitional cell carcinomas obtained by a transurethral resection. In the patients with superficial tumours, disease-free survival (DFS) was positively influenced by good histological differentiation as well as by concurrent high p27Kip1 and low Ki-67 expression. Multivariate analysis has confirmed that tumour grade and p27Kip1/Ki-67 status were independent predictors of DFS (p=0.028 and p=0.029, respectively). P27Kip1 or Ki-67 expressions did not influence overall survival. We conclude that a variable combined of p27Kip1 and Ki-67 expressions is a better predictor of DFS in superficial bladder tumours than either protein alone.

Bladder flap for reconstruction of congenital absence of the vagina.

An original method for vaginal reconstruction, using a pedunculated bladder wall flap is described. The method can be applied for vaginal reconstruction in cases of congenital absence or hypoplasia, as well as in cases of male transsexualism. 4 patients have been operated by this method without complications. In 2 patients, with 11 and 8 months follow-up, the results are satisfactory. The authors clearly describe the technical method of operation.

The presence of prostate cancer at biopsy is predicted by a number of genetic variants

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low‐risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.